HUMAN LEPTIN FORMS COMPLETES WITH ALPHA-2-MACROGLOBULIN WHICH ARE RECOGNIZED BY THE ALPHA-2-MACROGLOBULIN RECEPTOR LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN/
G. Birkenmeier et al., HUMAN LEPTIN FORMS COMPLETES WITH ALPHA-2-MACROGLOBULIN WHICH ARE RECOGNIZED BY THE ALPHA-2-MACROGLOBULIN RECEPTOR LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN/, European journal of endocrinology, 139(2), 1998, pp. 224-230
Objective: To identify binding proteins of leptin in human plasma. Met
hods: Binding was evaluated by electrophoresis, size exclusion chromat
ography (SEC), Western blotting, and radioisotope labeling. Quantifica
tion of leptin and the different forms of alpha 2-macroglobulin (alpha
2-M) was performed by ELISA. Results: Leptin interacts with the prote
inase inhibitor, alpha 2-M. I-125-labeled leptin specifically binds to
the transformed inhibitor, which arises by reaction with proteinases
or with reactive primary amines. No leptin binding was observed to the
native alpha 2-M, which abundantly occurs in plasma. The complex form
ation between leptin and alpha 2-M was found to proceed within minutes
and was stable, as it resisted separation by SEC and electrophoresis.
The lid of the complex was 2.14 +/- 0.75 mu mol/l. Complex formation
with transformed alpha 2-M did not interfere with the immunological de
termination of leptin in plasma. The leptin-alpha 2-M complex was foun
d to be recognized by the alpha 2-M receptor/low density lipoprotein r
eceptor-related protein. By computer analysis, a simple model is prese
nted showing that the degree of transformation of alpha 2-M may signif
icantly influence the leptin concentration in blood. Conclusions: The
proteinase inhibitor, alpha 2-M, may act as a leptin-binding protein i
n human plasma, finding of leptin to transformed alpha 2-M and its rap
id clearance by the alpha 2-M receptor may significantly influence the
bioavailability of leptin in human plasma.